Molecular chaperones, also known as heat shock proteins (Heat shock protein, Hsp) act to prevent aggregation and improper folding of proteins. The incorrect folding of the protein causes loss of function, as in some types of cancer and neurodegenerative diseases, and reduce life expectancy. These deleterious effects motivate the development of compounds that may, for instance, induce the expression or modulate the function of molecular chaperones. Thus, the study of the interaction between proteins and the search for compounds that can modulate the function of chaperones has become extremely important for the advancement of scientific knowledge on different cellular mechanisms and in searching for new drugs to increase the production of proteins properly folded. The chaperone Hsp90 is important for cell physiology, because it is involved in the stabilization of several proteins involved in signaling, and has recently been implicated in the stabilization of the tumor phenotype of various cancers. The interaction with co-chaperones, auxiliary proteins, enables Hsp90 to act as a hub, i.e. a central point of regulation of several proteins, and thus to regulate several pathways. The intervention in the interaction of Hsp90 co-chaperone is therefore a potentially effective strategy to intervene in the function of this chaperone. Many of these co-chaperones have a domain named TPR that interact with a specific MEEVD motif located in the C-terminus of Hsp90. Our goal is to use the technique of isothermal titration microcalorimetry (ITC) to characterize the thermodynamics of interactions between this peptide and several co-chaperones containing TPR domain to generate knowledge towards the development of intervention strategies in the interaction between these proteins. Our proposal is also supported on previous results from our group on the thermodynamic characterization of the interaction of the C-terminal domain of Hsp90 co-chaperone with a TPR.
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